title: Angiotensin II regulates collagen metabolism through modulating   tissue inhibitor of metalloproteinase-1 in diabetic skin tissues.
abstract: We investigated the effect of angiotensin II (Ang II) on matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) balance in regulating collagen metabolism of diabetic skin. Skin tissues from diabetic model were collected, and the primary cultured fibroblasts were treated with Ang II receptor inhibitors before Ang II treatment. The collagen type I (Coll I) and collagen type III (Coll III) were measured by histochemistry. The expressions of transforming growth factor-β (TGF-β), MMP-1, TIMP-1 and propeptides of types I and III procollagens in skin tissues and fibroblasts were quantified using polymerase chain reaction (PCR), Western blot or enzyme-linked immunosorbent assay (ELISA). Collagen dysfunction was documented by changed collagen I/III ratio in streptozotocin (STZ)-injected mice compared with controls. This was accompanied by increased expression of TGF-β, TIMP-1 and propeptides of types I and III procollagens in diabetic skin tissues. In primary cultured fibroblasts, Ang II prompted collagen synthesis accompanied by increases in the expressions of TGF-β, TIMP-1 and types I and III procollagens, and these increases were inhibited by losartan, an Ang II type 1 (AT1) receptor blocker, but not affected by PD123319, an Ang II type 2 (AT2) receptor antagonist. These findings present evidence that Ang-II-mediated changes in the productions of MMP-1 and TIMP-1 occur via AT1 receptors and a TGF-β-dependent mechanism.
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ren
authors.forename: Shaoyun
authors.initials: S
authors.lastname: Hao
authors.forename: Chuan
authors.initials: C
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.forename: Diaozhu
authors.initials: D
authors.lastname: Lin
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Yan
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005347:Fibroblasts / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D000804:Angiotensin II; D003094:Collagen; D020781:Matrix Metalloproteinase 1